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Biomedical subjects

P Braun

Publications and source records attributed to P Braun.

At least 37 records · Page 2Linked to original sources
PubMed2000

The potential to use PspA and other pneumococcal proteins to elicit protection against pneumococcal infection.

Pneumococcal proteins, alone, in combination with each other, or in combination with capsular polysaccharide-protein conjugates may be useful pneumococcal vaccine components. Four proteins with a potential for use in vaccines are PspA, pneumolysin, PsaA, and PspC. In a mouse model of carriage, PsaA and PspC were the most efficacious vaccine proteins. Of these, PsaA was the best at eliciting protection against carriage. However, a combination of PspA and pneumolysin may elicit stronger immunity to pulmonary infection and possibly sepsis than either protein alone. Recently, a phase one trial of a recombinant family 1 PspA was completed in man. PspA was observed to be safe and immunogenic. Injection of 0.1 ml of immune serum diluted to 1/400 was able to protect mice from fatal infection with S. pneumoniae. Under these conditions, pre-immune serum was not protective. The immune human serum protected mice from infections with pneumococci expressing either of the major PspA families (1 and 2) and both of the pneumococcal capsular types tested: 3 and 6.

Adult↗
PubMed2000

[Volumetry of the urinary bladder with implantable ultrasound sensors].

Experimental studies revealed that the contractile response of the urinary bladder to sacral anterior root stimulation depends on the actual bladder volume. Furthermore, no clinical relevant technique is available for continuous monitoring of the bladder wall distension respectively bladder volume in paraplegic patients. The presented study investigates the reliability of especially developed implantable ultrasound sensors as a sensoric system for continuous monitoring of the bladder volume. In six anaesthesized pigs two ultrasound sensors, one transmitter and one receiver, were implanted on the bladder wall at different locations (latero-lateral, dorsal-ventral, rostral-caudal). After closing the abdominal wall, the bladder was filled in 50 ml steps up to 250 ml. After each filling step the running time of the ultrasound signal was measured. In all experiments reproducible results and a high correlation of the measured running times with bladder volume were observed. The latero-lateral configuration of the sensors seemed to be most confidential. The presented study indicates that bladder volumetry with implantable ultrasound sensors is possible with minimal technical prerequisites. This promising technique for continuous bladder volumetry could play an important role in the development of an intelligent and autoadaptive neurostimulator of the urinary bladder in paraplegic patients.

Animals↗
PubMed2000

Occult micro medullary thyroid carcinoma: therapeutic strategy and follow-up.

Twenty micro medullary thyroid carcinomas (MTCs) were found in histologic specimens of 19 patients in our department from 1990 to 1998. There were 14 women and 5 men, with a median age of 63 years. The indication for surgery was goiter in 12 patients and a solitary nodule in 7 patients (three differentiated cancers). Altogether, 18 patients had unifocal micro-MTCs with a median diameter of 3.6 mm. One patient had a bilateral MTC (3 and 5 mm, respectively). Surgical procedures consisted of 9 total thyroidectomies and 10 lobectomies or subtotal thyroidectomies. Of these 10 patients, 4 underwent reoperation (totalization). One was operated on 48 months after a positive pentagastrin test: There was no thyroid residual tumor but three lymph node micrometastases. Among the six patients in whom thyroid tissue was left, a 91-year-old woman died of unrelated cause and the five others remain disease-free without biologic abnormalities at follow-ups of 18 to 70 months. Considering the aggressiveness of MTCs, total thyroidectomy with central compartment dissection is theoretically indicated. However, among the nine total thyroidectomies and four secondary totalizations associated with at least central compartment dissection, no other thyroid lesion was observed and only one case of lymph node microinvasion was found. Because of the morbidity associated with reoperation and neck dissection, we propose that it is indicated only for microcarcinomas > 5 mm in diameter, in cases of an abnormal response to pentagastrin, or when it is difficult to ensure prolonged follow-up of the patient.

Adult↗
PubMed1999

[Persistence of Chlamydia pneumoniae in coronary plaque tissue. A contribution to infection and immune hypothesis in unstable angina pectoris].

BACKGROUND AND OBJECTIVE: There is an increasing number of pointers towards a causative connection between Chlamydia pneumoniae and atherosclerosis. But the pathogenetic mechanism and intimal structures that are involved remain unclear. Starting with the hypothesis of a chronic infection, as demonstrated by the presence of the chlamydial stress (heat-shock) protein 60 (HSP 60), the presence and localization of these bacterial products in coronary atheromas was investigated. PATIENTS AND METHODS: Coronary atheroma tissue from primary stenoses in 42 patients (36 men, 6 women, mean age 60.2 +/- 7.3 years) was studied immunohistochemically in the course of a retrospective analysis for chlamydial HSP 60. The findings in clinically acute coronary syndrome (Braunwald's classification) present in 27 patients were compared with those in 15 patients with acute angina and evaluated in relation to expression and site of predilection. RESULTS: An immune reaction to chlamydial HSP 60 was demonstrated in 27 of 42 atheromas (64%). Intact, non-atherosclerotic vessels, such as the mammary artery and sphenous vein, showed no such signals. Chlamydial HSP 60 was localized in maximally 23% of all plaque cells, mostly in macrophages/foam cells, more rarely in smooth muscle cells. Chlamydia in foam cells most often revealed ultrastructural patterns that pointed to the persistence of the pathogen. Sites of predilection of chlamydial HSP were predominantly foam cell areas and cell-poor regions, more rarely inflammatory infiltrates and areas of rupture. When comparing both types of lesion, signals for chlamydial HSP 60 were present in 21 of the 27 atheromas (78%) with unstable angina or acute myocardial infarction, but in only 6 of the 15 atheromas (40%) with stable angina. Within the group with the acute coronary syndrome, the prevalence of chronic chlamydial infection was independent of a previous myocardial infarction. CONCLUSIONS: Chlamydial HSP 60 can often be demonstrated in primary coronary stenosis of symptomatic patients. It is most frequently found in macrophages/foam cells and is highly prevalent in the acute coronary syndrome. In-situ findings suggest a pathogenetically relevant role of chronic persistent infection of Chlamydia pneumoniae in unstable coronary plaques.

Adult↗
PubMed1999

The aromatic residues Trp and Phe have different effects on the positioning of a transmembrane helix in the microsomal membrane.

We have examined the effect of Trp and Phe residues on the positioning of a poly-Leu transmembrane helix relative to the microsomal membrane by employing a previously described "glycosylation mapping" technique [Nilsson, I. M., Sääf, A., Whitley, P., Gafvelin, G., Waller, C., and von Heijne, G. (1998) J. Mol. Biol. 284, 1165-1175]. Both Trp and Phe tend to push the transmembrane helix into the membrane when inserted in positions flanking the poly-Leu stretch, and Trp (but not Phe) pulls the transmembrane helix toward the lipid-water interface when inserted inside the poly-Leu segment. Thus, the preference of Trp for the lipid-water interface previously suggested on the basis of biophysical studies of model peptides can also be observed for a bona fide transmembrane helix in a biological membrane. We further show that a sufficiently long poly-Trp segment functions as an efficient stop-transfer sequence during protein translocation across the microsomal membrane, despite the preference of Trp residues for the lipid-water interface region.

Bacterial Proteins↗
PubMed1999

Recording the evoked canine detrusor electromyogram.

With increasing interest in detrusor disorders and possible detrusor myopathies, a method for recording the detrusor electromyogram (detrusor-EMG) would probably greatly assist the diagnosis of various bladder dysfunctions. Therefore, we investigated the electromyographic activity of the detrusor during sacral root stimulation and during spontaneous bladder contractions in six anesthetized dogs. In all experiments, a high correlation of detrusor-EMG recordings with bladder contraction was observed. Analysis in the time domain and power spectrum analysis revealed the most clear correlation of detrusor-EMG with intravesical pressure rise in a frequency band above 3 Hz. The spike duration was 100 to 250 ms with an amplitude of 100 to 500 microV. Low-frequency activity below 1 Hz was mainly presumed to be artifacts due to fluid movement under the electrode. Our trials indicate that smooth muscle EMG recordings from the detrusor smooth musculature are possible. The exact physiological relevance of the signal in the sub-Hertz domain (<1 Hz) is still uncertain. The presented animal model allows the pathophysiologic investigation of various pathologies of bladder dysfunction and detrusor myopathies. Neurourol. Urodynam. 18:687-695, 1999.

Animals↗
PubMed1999

[Coil embolization of an AV-fistula between the left thoracic artery and vein after coronary artery bypass surgery].

We report a case of an artificial fistula between the internal thoracic artery and vein after coronary artery bypass surgery, anastomosing the left internal thoracic artery to the LAD. Because of symptomatic anterior wall ischaemia due to coronary steal a treatment was mandatory. Instead of surgical correction, this shunt was closed by coil embolization of the venous limb.

Arteriovenous Fistula↗
PubMed1999

Improving protein secretion by engineering components of the bacterial translocation machinery.

The increased insight into the mechanism of bacterial protein translocation has resulted in new concepts for the production of heterologous proteins. The periplasm of gram-negative bacteria is revealed to have a role as a 'protein construction compartment', which can be used to fold complex proteins. Passage across the outer membrane, however, remains a challenge due to the high selectivity of the outer membrane translocase. In gram-positive bacteria, slow folding at the membrane-cell-wall interface can make heterologous proteins vulnerable to degradation by wall-associated proteases. The recent identification of thiol-disulfide oxidoreductases in Bacillus subtilis might open the possibility of secreting proteins containing multiple disulfide bonds from this host.

Bacillus subtilis↗
PubMed1999

Information needs in a changing health care system: capitation and the need for a population-oriented view.

Information systems needed for managing the health care of populations under at-risk (capitation) contracts must be designed differently than those used in fee-for-service practice. Under capitation, providers must deliver health care to enrollees with financial resources that are fixed in advance. Therefore, the information systems they use must enable them to understand the health status of health plan enrollees and how health care is provided. These systems should facilitate the detection of underservice and of inadequate quality of health care as well as overuse of health care resources. They should permit clinical-epidemiologic and statistical analysis; facilitate disease management and the adoption of preventive programs, and lend themselves to use by planners, group leaders, and practicing physicians.

Ambulatory Care Information Systems↗
PubMed1998

Effect of HELP-LDL-apheresis on outcomes in patients with advanced coronary atherosclerosis and severe hypercholesterolemia.

In the secondary prevention of coronary artery disease (CAD) the beneficial effect of lipid lowering is no longer controversial. LDL-apheresis is a feasible therapy for effective lipid lowering in patients refractory to diet and cholesterol lowering drugs. To assess the impact of the HELP-therapy (heparin-induced, extracorporeal LDL precipitation) on patients' clinical outcome and coronary angiography, we set up a prospective trial, in which patients with advanced coronary atherosclerosis and severe hypercholesterolemia resistant to diet and drug therapy were treated with LDL-apheresis. A total of 44 patients were treated with adjunctive weekly HELP-therapy for 15.5 +/- 9.5 months. The mean levels of total cholesterol (Chol), LDL-cholesterol (LDL-C), Lp(a), and fibrinogen at baseline were 308.0 +/- 69.7, 231.8 +/- 72.7, 82.2 +/- 54.1, and 356.1 +/- 94.1 mg/dl, respectively. LDL-apheresis caused a mean per treatment reduction of 44.8 +/- 8.7, 55.5 +/- 8.6, 60.8 +/- 10.2, and 53.8 +/- 6.5% of Chol, LDL-C, Lp(a), and fibrinogen, resulting in mean treatment interval values of 190.4 +/- 33.7, 116.3 +/- 28.9, 51.9 +/- 33.1, and 213.7 +/- 148.9 mg/dl, respectively. Improvement of the clinical status (exercise tolerance, anti-anginal drug use, angina pectoris) was found in 73%, no change in 11%, and deterioration in 16% of the cases. Four patients died cardiac death. The maximal bicycle exercise work load of the patients increased significantly from 101 +/- 41 to 119 +/- 46 W (P < 0.001). Ten (40%) out of 25 patients who underwent follow-up angiography revealed CAD progression, whereas two (8%) patients had CAD regression. Despite angiographic deterioration eight out of ten progressors (80%) improved clinically. In patients with advanced coronary atherosclerosis and severe hypercholesterolemia HELP-therapy can safely and effectively lower LDL-C, Lp(a), and fibrinogen. The chronic weekly HELP-treatment results in clinical improvement in the majority of patients, even in those patients with angiographically shown CAD progression.

Adult↗
PubMed1998

Effects of glycosylation on fragments of tumour associated human epithelial mucin MUC1.

The glycodecapeptide AcPAPGS(alpha GalNAc)T(alpha GalNAc)APPA and the C-terminal glycohexapeptide AcS(alpha GalNAc)T(alpha GalNAc)APPA have been synthesized by applying the N-terminal Fmoc group in combination with the heptyl ester cleavable by lipase-catalyzed hydrolysis at pH 7. The solution conformation of these MUC1-related synthetic glycopeptides and the control, non-glycosylated decapeptide AcPAPGSTAPPA have been investigated using NMR spectroscopy. The structural studies indicate that the glycohexapeptide has a folded structure in solution. For this molecule, unrestrained molecular dynamics has been used to confirm the presence of the observed solution through-space connections. The results indicate that the non-globular nature of MUC1 is due to both protein core sequence and the effect of carbohydrate.

Amino Acid Sequence↗
PubMed1998

Secretion of elastinolytic enzymes and their propeptides by Pseudomonas aeruginosa.

Elastase of Pseudomonas aeruginosa is synthesized as a preproenzyme. The signal sequence is cleaved off during transport across the inner membrane and, in the periplasm, proelastase is further processed. We demonstrate that the propeptide and the mature elastase are both secreted but that the propeptide is degraded extracellularly. In addition, reduction of the extracellular proteolytic activity led to the accumulation of unprocessed forms of LasA and LasD in the extracellular medium, which shows that these enzymes are secreted in association with their propeptides. Furthermore, a hitherto undefined protein with homology to a Streptomyces griseus aminopeptidase accumulated under these conditions.

Bacterial Proteins↗
PubMed1998

[Combined effect of temperature a(W) and pH on proteases from Pseudomonas and Bacillus spp].

The factors affecting protease activity were investigated on certain media. Five strains of Bacillus (B.) cereus, four strains of B. subtilis, five strains of Pseudomonas (Ps.) aeruginosa and two strains of Ps. fluorescens produced the proteases that were tested. The enzyme activity was evaluated under 32 different combinations of temperature (2 and 7 degrees C), water activity (aw) (0.80-0.98) and pH (4.0-7.3). A decrease in water activity and pH and/or temperature caused a decrease in protease activity. It appeared that the combined effect of temperature, aw and pH influences enzyme production significantly compared with the influence of single environmental factors. Temperature plays the crucial role in these reactions. Enzyme activities could be observed even at low temperature. Although the exoprotease of Ps. spp. showed intense activity at refrigeration temperature, low pH and aw, Bacillus proteases were comparably less active under the same conditions, but nevertheless proved to be significant.

Bacillus cereus↗
PubMed1998

Long-term followup and selection criteria for penile revascularization in erectile failure.

PURPOSE: We report the long-term results of penile revascularization surgery for erectile failure and suggest possible selection criteria for this controversial surgical procedure. MATERIALS AND METHODS: In 7 years 62 impotent men who did not respond to pharmacotherapy underwent microsurgical penile revascularization and completed long-term followup evaluation in 41 months (range 18 to greater than 62) consisting of a detailed questionnaire, duplex sonography and optional pharmacotherapy or angiography. The Virag procedure was chosen for the first 7 patients, the original Hauri technique for the next 13 and the modified Mannheim triple anastomosis for 42. RESULTS: Of all patients 34% achieved spontaneous and another 20% pharmacologically induced erections. Success in diabetics and older patients was lower (43% for diabetics, 39% for those older than 50 years at surgery), while it was high in men with less than 2 risk factors (58%) as well as in younger patients (69% for those up to 50 years old). Shunt patency was 92%. Complications such as glans hyperemia developed in 13% of patients, shunt thrombosis in 8% and inguinal hernias in 6.5%. CONCLUSIONS: Patient selection is vital for the successful outcome of penile revascularization surgery. We adhere to strict selection criteria, such as patient age maximum of 50 years, less than 2 risk factors, no recent diabetes and termination of nicotine abuse. Penile revascularization surgery is highly indicated in this group of patients, especially since it is the only causal therapy for erectile failure.

Adult↗
PubMed1997

Alanine insertion scanning mutagenesis of lactose permease transmembrane helices.

A priori, single residue insertions into transmembrane helices are expected to be highly disruptive to protein structure and function. We have carried out a systematic analysis of the phenotypes associated with Ala insertions into transmembrane helices in lactose permease, a multispanning Escherichia coli inner membrane protein. Insertion of alanine into the center of 7 transmembrane helices was found to abolish stable integration of lactose permease into the membrane or uphill lactose transport. A more detailed Ala insertion scan was made of transmembrane helix III. The results pin-point a central region of approximately 2 helical turns that is crucial for lactose permease stability and/or activity. A Trp scan in this region identified 2 residues essential for lactose permease stability. From these results, it appears that transmembrane helices have differential sensitivities to single residue insertions and that such mutations may be useful for identifying structurally and/or functionally important helix segments.

Alanine↗
PubMed1997

SAPALDIA: methods and participation in the cross-sectional part of the Swiss Study on Air Pollution and Lung Diseases in Adults.

SAPALDIA--the Swiss Study on Air Pollution and Lung Diseases in Adults--focuses on the long term health effects of low to moderate levels of air pollutants as typically seen in different parts of Switzerland. The aim of the SAPALDIA cross-sectional study carried out in 1991 was to determine the prevalence of bronchial asthma, chronic bronchitis and allergic conditions in the adult population of Switzerland and to identify and to determine the respective importance of potentially influencing factors. These could be both personal (smoking habits, allergy status, family history, occupation) and environmental (outdoor and indoor pollution, aeroallergens, climate). A further aim of the cross-sectional study consisted in the identification of individuals susceptible to present symptoms during a two year observation period and to be included in the SAPALDIA follow-up study. This technical report represents the methodological documentation for the cross-sectional study of SAPALDIA. The instruments and the methods of standardisation are presented and discussed. The medical examination consisted of a computerised interview using a standardised questionnaire, the taking of a blood sample for serological tests, allergy skin testing, the measurement of end expiratory CO and body height, and pulmonary function testing followed by methacholine challenge testing or bronchodilatation testing. The pattern of participation and the 9651 participants of the study, representing 59.3% of the sample, are described. Based on information on non-participants gained by telephone interviews and mailed short questionnaires, possible selection biases are quantified and discussed.

Adult↗